Melanoma is the most serious form of skin cancer and early diagnosis is the best way to combat it. Distinguishing benign pigmented lesions from early melanomas can be difficult. Smell or odor has been used as a symptom of disease for centuries. The evidence for the extreme olfactory ability of canines, both in terms of detection threshold and in terms of ability to detect cancer has been documented. The goal of this project is to directly demonstrate that canine olfactory receptors respond to melanoma tumor markers (volatile compounds). The central hypothesis is that melanoma tissue contains unique volatiles - biomarkers that can be recognized by olfactory receptors. Melanoma volatiles from human biopsy samples will be profiled by gas chromatography and mass spectrometry. The major innovation of this proposal is to lay foundation for the clinical diagnosis of melanoma based on volatile by-products of altered metabolism. The bilaterally symmetrical olfactory epithelium will be divided into subsections. Membrane sheets containing receptors isolated from the left side of the epithelium will be injected into Xenopus oocytes and tested by high throughput electrophysiology against isolated melanoma biomarkers. The genetic identify of the canine olfactory receptors will be determined using microarray analysis of mRNA isolated from the parallel subsections on the right side. After identification, candidate canine olfactory receptors will be pharmacologically characterized in heterologous expression system. Identification of the specific canine olfactory receptors that recognize melanoma markers will enable pursuit of our long-term objective: the development of a safe and non-invasive diagnostic tool - a biosensor for the early detection of melanoma. PUBLIC HEALTH RELEVANCE: Melanoma is the most serious form of skin cancer, and early diagnosis is the best strategy to combat it. The goal of this project is to identify canine olfactory receptors that recognize volatile compounds - biomarkers present is human melanoma in order to develop diagnostic screen assay - a biosensor, for its early detection.